Aging is associated with decline in immunological vigor which can contribute to development of age-associated disease and can lengthen the after-illness recovery period in the elderly. Nutritional manipulation of the aged immune system is the most practical and inexpensive approach to improving the immune response. Yet, indepth studies concerning nutrition and the immune system, especially as it relates to aging, are only beginning. Vitamin E and polyunsaturated fatty acids impact normal immune function, and megadoses of vitamin E are immuno-stimulatory. However, the interaction of vitamin E and polyunsaturated fatty acids, especially the subtle differences between the physiological and pharmacological roles of tocopherol and polyunsaturated fatty acid-containing oils on immune function, and the mechanisms of their action is not understood. Vitamin E presumably functions through I2 T-cells and their release of factors (e.g., PG, IL2) that influence T or B-lymphocytes. In order to develop the appropriate model for study of these relationships, these initial studies will determine the interaction between different types of dietary fat and vitamin E on immune function in young and old mice to obtain a reasonable measure of the controlling mechanisms involved. This will be accomplished by study of phospholipids and the cyclooxygenase and lipooxygenase pathways of arachidonic acid and eicosapentaenoic acid metabolism. In vivo antibody response to SRBC, skin sensitization response to DNFB, and in vitro blastogenic response of splenocytes to T and B-cell mitogens will be measured and correlated with vitamin E level, phospholipid fatty acid profile, ability of spleen cells to produce PGE2, TXB2, 12-HETE, TBA, and T-cell growth factor. To further separate the antioxidant mechanism from the more subtle control of PG metabolism, the effect of vitamin E on the immune system of young and old mice will be compare to that of ethoxyquin (an antioxidant) and indomethacin (a cyclooxygenase inhibitor). By supplying different fatty acid substrates in the form of dietary fats and manipulating the PG-LT metabolic pathway by antioxidant or pharmacological means under these conditions, three tasks will be accomplished: 1) a general mechanism of tocopherol function in the immune system can be delineated, 2) the association between structural properties of different dietary fatty acids on immune function in relation to the vitamin E requirement will be revealed, 3) the potential role of tocopherol and dietary fats on altering immune function in aged animals will be determined.